Tricoastal Narcolepsy and Sleep Disorders Center, Sugar Land, TX, USA.
Harmony Biosciences, LLC, Plymouth Meeting, PA, USA.
CNS Drugs. 2022 Jan;36(1):61-69. doi: 10.1007/s40263-021-00886-x. Epub 2021 Dec 21.
Pitolisant, a selective histamine 3 receptor antagonist/inverse agonist, is indicated for the treatment of excessive daytime sleepiness or cataplexy in adults with narcolepsy. The efficacy and safety of pitolisant have been demonstrated in randomized placebo-controlled trials. When evaluating the results of randomized placebo-controlled trials, the clinical impact of a treatment can be assessed using effect size metrics that include Cohen's d (the standardized mean difference of an effect) and number needed to treat (NNT; number of patients that need to be treated to achieve a specific outcome for one person).
The objective of this study was to evaluate the clinical impact of pitolisant for the reduction in excessive daytime sleepiness or cataplexy in adults with narcolepsy.
This post hoc analysis incorporated data from two 7-week or 8-week randomized placebo-controlled trials (HARMONY 1, HARMONY CTP). Study medication was individually titrated, with a maximum possible pitolisant dose of 35.6 mg/day. Efficacy was assessed using the Epworth Sleepiness Scale (ESS) and weekly rate of cataplexy (HARMONY CTP only). Cohen's d was derived from the least-squares mean difference between treatment groups (pitolisant vs placebo), and NNTs were calculated from response rates. Treatment response was defined for excessive daytime sleepiness in two ways: (a) reduction in ESS score ≥ 3 or final ESS score ≤ 10 and (b) final ESS score ≤ 10. Treatment response was defined for cataplexy as a ≥ 25%, ≥ 50%, or ≥ 75% reduction in weekly rate of cataplexy.
The analysis population included 61 patients in HARMONY 1 (pitolisant, n = 31; placebo, n = 30) and 105 patients in HARMONY CTP (pitolisant, n = 54; placebo, n = 51). For pitolisant vs placebo, Cohen's d effect size values were 0.61 (HARMONY 1) and 0.86 (HARMONY CTP) based on changes in ESS scores, and 0.86 (HARMONY CTP) based on changes in weekly rate of cataplexy. NNTs for pitolisant were 3-5 for the treatment of excessive daytime sleepiness and 3-4 for the treatment of cataplexy.
The results of this analysis demonstrate the robust efficacy of pitolisant for the reduction in both excessive daytime sleepiness and cataplexy. These large effect sizes and low NNTs provide further evidence supporting the strength of the clinical response to pitolisant in the treatment of adults with narcolepsy.
ClinicalTrials.gov identifiers: NCT01067222 (February 2010), NCT01800045 (February 2013).
哌甲酯是一种选择性组胺 3 受体拮抗剂/反向激动剂，适用于治疗成人嗜睡症或猝倒。哌甲酯的疗效和安全性已在随机安慰剂对照试验中得到证实。在评估随机安慰剂对照试验的结果时，可以使用包括 Cohen's d（效应的标准化均数差）和需要治疗的人数（NNT；为一个人实现特定结果需要治疗的患者人数）在内的效应大小指标来评估治疗的临床影响。
本研究旨在评估哌甲酯对成人嗜睡症患者嗜睡或猝倒的减少的临床影响。
这项事后分析纳入了两项为期 7 周或 8 周的随机安慰剂对照试验（HARMONY 1、HARMONY CTP）的数据。研究药物进行个体化滴定，哌甲酯最大可能剂量为 35.6mg/天。使用 Epworth 嗜睡量表（ESS）和每周猝倒率（仅 HARMONY CTP）评估疗效。Cohen's d 源自治疗组之间的最小二乘均数差异（哌甲酯与安慰剂），NNT 则从反应率计算得出。两种方法定义了日间嗜睡的治疗反应：（a）ESS 评分降低≥3 或最终 ESS 评分≤10 和（b）最终 ESS 评分≤10。猝倒的治疗反应定义为每周猝倒率降低≥25%、≥50%或≥75%。
分析人群包括 HARMONY 1 中的 61 名患者（哌甲酯，n=31；安慰剂，n=30）和 HARMONY CTP 中的 105 名患者（哌甲酯，n=54；安慰剂，n=51）。与安慰剂相比，哌甲酯的 Cohen's d 效应大小值为 0.61（HARMONY 1）和 0.86（HARMONY CTP），基于 ESS 评分的变化，以及 0.86（HARMONY CTP），基于每周猝倒率的变化。哌甲酯治疗日间嗜睡的 NNT 为 3-5，治疗猝倒的 NNT 为 3-4。
本分析结果表明，哌甲酯对减少嗜睡症和猝倒均具有显著疗效。这些较大的效应大小和较低的 NNT 进一步证明了哌甲酯治疗成人嗜睡症的临床反应强度。
ClinicalTrials.gov 标识符：NCT01067222（2010 年 2 月），NCT01800045（2013 年 2 月）。
